View source for Myasthenia gravis

{{Short description|Autoimmune disease resulting in skeletal muscle weakness}}
{{Use dmy dates|date=June 2025}}
{{Infobox medical condition
| name = Myasthenia gravis
| image = DiplopiaMG1.jpg
| caption = [[Strabismus|Eye deviation]] and a [[ptosis (eyelid)|drooping eyelid]] in a person with myasthenia gravis trying to open her eyes
| field = [[Neurology]]
| symptoms = Varying degrees [[muscle weakness]], [[diplopia|double vision]], [[ptosis (eyelid)|drooping eyelid]]s, trouble talking, trouble walking<ref name="NIH2016" />
| complications =
| onset = Women under 40, men over 60<ref name="NIH2016" />
| duration = Long term<ref name="NIH2016" />
| causes = [[Autoimmune disease]]<ref name="NIH2016" />
| risks =
| diagnosis = Blood tests for specific [[antibodies]], [[edrophonium test]], [[nerve conduction studies]]<ref name="NIH2016" />
| differential = [[Guillain–Barré syndrome]], [[botulism]], [[organophosphate poisoning]], [[brainstem stroke]],<ref>{{Cite book |url=https://books.google.com/books?id=fSlFA8B24FgC&pg=PA118 |title=In a Page: Neurology |vauthors=Kahan S |date=2005 |publisher=Lippincott Williams & Wilkins |isbn=978-1-4051-0432-6 |page=118 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=fSlFA8B24FgC&pg=PA118 |archive-date=8 September 2017 |url-status=live}}</ref> [[Metabolic myopathy|metabolic myopathies]]
| prevention =
| treatment = Medications, [[thymectomy|surgical removal of the thymus]], [[plasmapheresis]]<ref name="NIH2016" />
| medication = [[Acetylcholinesterase inhibitor]]s ([[neostigmine]], [[pyridostigmine]]), [[immunosuppressants]]<ref name="NIH2016" />
| prognosis =
| frequency = 50 to 200 per million<ref name="Kam2009" /><ref name="Adams2012" />
| deaths =
}}
<!-- Definition and symptoms -->

'''Myasthenia gravis''' ('''MG''') is a long-term [[neuromuscular junction disease]] that leads to varying degrees of skeletal [[muscle weakness]].<ref name="NIH2016" /> The most commonly affected muscles are those of the [[eye]]s, [[facial muscles|face]], and swallowing.<ref name="NIH2016" /><ref name="auto1">{{Cite journal |display-authors=6 |vauthors=Salari N, Fatahi B, Bartina Y, Kazeminia M, Fatahian R, Mohammadi P, Shohaimi S, Mohammadi M |date=December 2021 |title=Global prevalence of myasthenia gravis and the effectiveness of common drugs in its treatment: a systematic review and meta-analysis |journal=Journal of Translational Medicine |volume=19 |issue=1 |article-number=516 |doi=10.1186/s12967-021-03185-7 |pmc=8686543 |pmid=34930325 |doi-access=free}}</ref> It can result in [[double vision]], [[drooping eyelid]]s, and difficulties in talking and walking.<ref name="NIH2016" /> Onset can be sudden.<ref name="NIH2016" /> Those affected often have a large [[thymus]] or develop a [[thymoma]].<ref name="NIH2016">{{Cite web |title=Myasthenia Gravis Fact Sheet |url=https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet |archive-url=https://web.archive.org/web/20210916071758/https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Myasthenia-Gravis-Fact-Sheet |archive-date=16 September 2021 |access-date=22 September 2021 |website=National Institute of Neurological Disorders and Stroke}}</ref>

<!-- Cause and diagnosis -->
Myasthenia gravis is an [[autoimmune disease]] of the neuromuscular junction which results from [[antibodies]] that block or destroy [[nicotinic acetylcholine receptor]]s (AChR) at the [[neuromuscular junction|junction between the nerve and muscle]].<ref>{{Cite report |url=https://www.ncbi.nlm.nih.gov/books/NBK571915/ |title=Rituximab for the Treatment of Myasthenia Gravis: A 2021 Update [Internet]. |date=April 2021 |publisher=Canadian Agency for Drugs and Technologies in Health |location=Ottawa (ON) |pmid=34255447 |access-date=27 January 2022 |archive-url=https://web.archive.org/web/20220707052128/http://www.ncbi.nlm.nih.gov/books/NBK571915/ |archive-date=7 July 2022 |url-status=live |vauthors=Young C, McGill SC}}</ref><ref>{{Cite journal |vauthors=Dabi A, Solieman N, Kurukumbi M, Kalyanam J |year=2012 |title=Myasthenia Gravis: A Review |journal=Autoimmune Diseases |volume=2012 |pages=1–10 |doi=10.1155/2012/874680 |pmc=3501798 |pmid=23193443 |doi-access=free}}</ref><ref name="NIH2016" /> This prevents [[nerve impulse]]s from triggering muscle contractions.<ref name="NIH2016" /> Most cases are due to immunoglobulin G1 (IgG1) and IgG3 antibodies that attack AChR in the postsynaptic membrane, causing complement-mediated damage and muscle weakness.<ref name="Pathogenesis of myasthenia gravis">{{Cite journal |vauthors=Phillips WD, Vincent A |date=1 January 2016 |title=Pathogenesis of myasthenia gravis: update on disease types, models, and mechanisms |journal=F1000Research |volume=5 |page=1513 |doi=10.12688/f1000research.8206.1 |pmc=4926737 |pmid=27408701 |doi-access=free}}</ref> Rarely, an inherited [[genetic defect]] in the [[neuromuscular junction]] results in a similar condition known as [[congenital myasthenia]].<ref name="Kandel2012">{{Cite book |title=Principles of Neural Science |vauthors=Kandel E, Schwartz J, Jessel T, Siegelbaum S, Hudspeth A |year=2012 |edition=5 |pages=318–319}}</ref><ref name="ReferenceA">{{Cite journal |vauthors=Vrinten C, van der Zwaag AM, Weinreich SS, Scholten RJ, Verschuuren JJ |date=December 2014 |title=Ephedrine for myasthenia gravis, neonatal myasthenia and the congenital myasthenic syndromes |journal=The Cochrane Database of Systematic Reviews |volume=2014 |issue=12 |article-number=CD010028 |doi=10.1002/14651858.CD010028.pub2 |pmc=7387729 |pmid=25515947}}</ref> Babies of mothers with myasthenia may have symptoms during their first few months of life, known as neonatal myasthenia<ref name="NIH2016" /> or more specifically [[transient neonatal myasthenia gravis]].<ref name="pmid38398450">{{Cite journal |vauthors=Lindroos JL, Bjørk MH, Gilhus NE |date=February 2024 |title=Transient Neonatal Myasthenia Gravis as a Common Complication of a Rare Disease: A Systematic Review |journal=Journal of Clinical Medicine |volume=13 |issue=4 |page=1136 |doi=10.3390/jcm13041136 |pmc=10889526 |pmid=38398450 |doi-access=free}}</ref> Diagnosis can be supported by blood tests for specific antibodies, the [[edrophonium test]], [[electromyography]] (EMG), or a [[nerve conduction study]].<ref name="NIH2016" />

<!-- Treatment -->
Mild forms of myasthenia gravis may be treated with medications known as [[acetylcholinesterase inhibitor]]s, such as [[neostigmine]] and [[pyridostigmine]].<ref name="NIH2016" /> [[Immunosuppressants]], such as [[prednisone]] or [[azathioprine]], may also be required for more severe symptoms that acetylcholinesterase inhibitors are insufficient to treat.<ref name="NIH2016" /> The [[thymectomy|surgical removal of the thymus]] may improve symptoms in certain cases.<ref name="NIH2016" /> [[Plasmapheresis]] and high-dose [[intravenous immunoglobulin]] may be used when oral medications are insufficient to treat severe symptoms, including during sudden flares of the condition.<ref name="NIH2016" /> If the breathing muscles become significantly weak, [[mechanical ventilation]] may be required.<ref name="NIH2016" /> Once [[intubated]] acetylcholinesterase inhibitors may be temporarily held to reduce airway secretions.<ref>{{Cite journal |vauthors=Godoy DA, Mello LJ, Masotti L, Di Napoli M |date=September 2013 |title=The myasthenic patient in crisis: an update of the management in Neurointensive Care Unit |journal=Arquivos de Neuro-Psiquiatria |volume=71 |issue=9A |pages=627–39 |doi=10.1590/0004-282X20130108 |pmid=24141444 |doi-access=free}}</ref>

<!-- Epidemiology, prognosis, and history -->
Myasthenia gravis affects 50 to 200 people per million.<ref name="Kam2009">{{Cite book |url=https://books.google.com/books?id=DampyXkudq8C&pg=PA72 |title=Myasthenia Gravis and Related Disorders |vauthors=Kaminski HJ |date=2009 |publisher=Springer Science & Business Media |isbn=978-1-59745-156-7 |edition=2 |page=72 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=DampyXkudq8C&pg=PA72 |archive-date=8 September 2017 |url-status=live}}</ref><ref name="Adams2012">{{Cite book |url=https://books.google.com/books?id=rpoH-KYE93IC&pg=PA844 |title=Emergency Medicine: Clinical Essentials |vauthors=Adams JG |date=2012 |publisher=Elsevier Health Sciences |isbn=978-1-4557-3394-1 |edition=2 |page=844 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=rpoH-KYE93IC&pg=PA844 |archive-date=8 September 2017 |url-status=live}}</ref> It is newly diagnosed in 3 to 30 people per million each year.<ref name="McG2010" /> Diagnosis has become more common due to increased awareness.<ref name="McG2010">{{Cite journal |vauthors=McGrogan A, Sneddon S, de Vries CS |year=2010 |title=The incidence of myasthenia gravis: a systematic literature review |journal=Neuroepidemiology |volume=34 |issue=3 |pages=171–183 |doi=10.1159/000279334 |pmid=20130418 }}</ref> Myasthenia gravis most commonly occurs in women under the age of 40 and in men over the age of 60.<ref name="NIH2016" /><ref name="auto1" /><ref name="auto2">{{Cite journal |vauthors=Conti-Fine BM, Milani M, Kaminski HJ |date=November 2006 |title=Myasthenia gravis: past, present, and future |journal=The Journal of Clinical Investigation |volume=116 |issue=11 |pages=2843–2854 |doi=10.1172/JCI29894 |pmc=1626141 |pmid=17080188}}</ref> It is uncommon in children.<ref name="NIH2016" /> With treatment, most live to an average [[life expectancy]].<ref name="NIH2016" /> The word is from the Greek ''mys'', "muscle" and ''asthenia'' "weakness", and the Latin ''gravis'', "serious".<ref>{{Cite book |url=https://books.google.com/books?id=o4HwCgAAQBAJ&pg=PA87 |title=Introduction to Medical Terminology |vauthors=Ehrlich A, Schroeder CL |date=2014 |publisher=Cengage Learning |isbn=978-1-133-95174-2 |page=87 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=o4HwCgAAQBAJ&pg=PA87 |archive-date=8 September 2017 |url-status=live}}</ref>

==Signs and symptoms==
The initial, main symptom in myasthenia gravis is painless [[Muscle weakness|weakness]] of specific muscles, not fatigue.<ref name="Engel2012">{{Cite book |last=Engel AG |url=https://books.google.com/books?id=V61KHl4T9vkC |title=Myasthenia Gravis and Myasthenic Disorders |date=2012 |publisher=Oxford University Press, US |isbn=978-0-19-973867-0 |edition=2nd |pages=109–110 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=V61KHl4T9vkC |archive-date=8 September 2017 |url-status=live}}</ref> The muscle weakness becomes progressively worse ([[Muscle fatigue|fatigue]]) during periods of physical activity and improves after periods of rest. Typically, the weakness and fatigue are worse toward the end of the day.<ref name="Scully2014">{{Cite book |last=Scully C |url=https://books.google.com/books?id=OZXdAwAAQBAJ |title=Scully's Medical Problems in Dentistry |publisher=Elsevier Health Sciences UK |year=2014 |isbn=978-0-7020-5963-6 |archive-url=https://web.archive.org/web/20170908162031/https://books.google.com/books?id=OZXdAwAAQBAJ |archive-date=8 September 2017 |url-status=live}}</ref> Myasthenia gravis generally starts with ocular (eye) weakness; it might then progress to a more severe generalized form, characterized by weakness in the extremities or in muscles that govern basic life functions.<ref name="Goldenberg">{{EMedicine|article|1171206|Myasthenia Gravis}}</ref>

===Eyes===
In about two-thirds of people, the initial symptom of myasthenia gravis is related to the muscles around the eye.<ref name="Engel2012" /> Eyelid drooping ([[ptosis (eyelid)|ptosis]] may occur due to weakness of m. [[levator palpebrae superioris]])<ref name="Nair2014" /> and double vision ([[diplopia]],<ref name="Engel2012" /> due to weakness of the [[extraocular muscles]]).<ref name="Scully2014" /> Eye symptoms tend to get worse when watching television, reading, or driving, particularly in bright conditions.<ref name="Engel2012" /> Consequently, some affected individuals choose to wear sunglasses.<ref name="Engel2012" /> The term "ocular myasthenia gravis" describes a subtype of myasthenia gravis where muscle weakness is confined to the eyes, i.e. extraocular muscles, m. levator palpebrae superioris, and m. [[orbicularis oculi]].<ref name="Nair2014" /> This subtype may evolve into generalized myasthenia gravis, usually after a few years.<ref name="Nair2014" /> If an individual with ocular myasthenia gravis does not generalize for three or more years after the onset of symptoms, then generalized myasthenia gravis is unlikely to occur.<ref>{{cite book |doi=10.1016/B978-1-4557-2376-8.00015-3 |chapter=Disorders of Ocular Motility |title=Fenichel's Clinical Pediatric Neurology |date=2013 |last1=Piña-Garza |first1=J. Eric |pages=295–312 |isbn=978-1-4557-2376-8 }}</ref>

===Eating===
The weakness of the muscles involved in swallowing may lead to swallowing difficulty ([[dysphagia]]). Typically, this means that some food may be left in the mouth after an attempt to swallow,<ref name="Scherer2005">{{Cite journal |vauthors=Scherer K, Bedlack RS, Simel DL |date=April 2005 |title=Does this patient have myasthenia gravis? |journal=JAMA |volume=293 |issue=15 |pages=1906–1914 |doi=10.1001/jama.293.15.1906 |pmid=15840866}}</ref> or food and liquids may regurgitate into the nose rather than go down the throat ([[velopharyngeal insufficiency]]).<ref name="Scully2014" /> Weakness of the muscles that move the jaw ([[muscles of mastication]]) may cause difficulty chewing. In individuals with myasthenia gravis, chewing tends to become more tiring when chewing tough, fibrous foods.<ref name="Engel2012" /> Difficulty in swallowing, chewing, and speaking is the first symptom in about one-sixth of individuals.<ref name="Engel2012" />

===Speaking===
Weakness of the muscles involved in speaking may lead to [[dysarthria]] and [[hypophonia]].<ref name="Engel2012" /> Speech may be slow and slurred,<ref name="Rajendran2014">{{Cite book |last1=Rajendran A |url=https://books.google.com/books?id=WnhtAwAAQBAJ&pg=P867 |title=Shafer's Textbook of Oral Pathology |last2=Sundaram S |date=2014 |publisher=Elsevier Health Sciences APAC |isbn=978-81-312-3800-4 |edition=7th |page=867 |archive-url=https://web.archive.org/web/20170402091932/https://books.google.com/books?id=WnhtAwAAQBAJ&pg=P867 |archive-date=2 April 2017 |url-status=live}}</ref> or have a [[Nasality (disorder)|nasal quality]].<ref name="Scully2014" /> In some cases, a singing hobby or profession must be abandoned.<ref name="Scherer2005" />

===Head and neck===
Due to weakness of the [[muscles of facial expression]] and muscles of mastication, facial weakness may manifest as the inability to hold the mouth closed<ref name="Engel2012" /> (the "hanging jaw sign") and as a snarling expression when attempting to smile.<ref name="Scully2014" /> With drooping eyelids, facial weakness may make the individual appear sleepy or sad.<ref name="Engel2012" /> Difficulty in holding the head upright may occur.<ref name="Rajendran2014" />

===Other===
The [[Muscles of respiration|muscles that control breathing]] and limb movements can also be affected; rarely do these present as the first symptoms of myasthenia gravis, but develop over months to years.<ref>{{MedlinePlusEncyclopedia|000712|Myasthenia gravis}}</ref> In a myasthenic crisis, a [[paralysis]] of the respiratory muscles occurs, necessitating [[assisted ventilation]] to sustain life.<ref name="Rosen2014">{{Cite book |title=Rosen's emergency medicine: concepts and clinical practice |vauthors=Marx JA |date=2014 |publisher=Elsevier/Saunders |isbn=978-1-4557-0605-1 |edition=8th |location=Philadelphia |pages=1441–1444}}</ref> Crises may be triggered by various biological stressors such as infection, fever, an adverse reaction to medication, or emotional stress.<ref name="Rosen2014" />

==Causes==
===Medications that cause or worsen myasthenia gravis===
[[Antibiotics]]: In the [[macrolide]] family of [[antibiotics]], [[azithromycin]], [[telithromycin]] (which is no longer available in the U.S. market), and [[erythromycin]] are reported to exacerbate myasthenia gravis. In the [[fluoroquinolone]] antibiotic family, [[ciprofloxacin]], [[norfloxacin]], [[ofloxacin]], and [[moxifloxacin]] are reported to exacerbate myasthenia gravis.<ref name="pmid33917535">{{Cite journal |vauthors=Sheikh S, Alvi U, Soliven B, Rezania K |date=April 2021 |title=Drugs That Induce or Cause Deterioration of Myasthenia Gravis: An Update |journal=Journal of Clinical Medicine |volume=10 |issue=7 |page=1537 |doi=10.3390/jcm10071537 |pmc=8038781 |pmid=33917535 |doi-access=free}}</ref> And, In the [[aminoglycoside]] family of antibiotics, [[gentamicin]], [[streptomycin]], and [[neomycin]] are reported to exacerbate myasthenia gravis.<ref name="pmid4568132">{{Cite journal |vauthors=Hall DR, McGibbon DH, Evans CC, Meadows GA |date=December 1972 |title=Gentamicin, tubocurarine, lignocaine and neuromuscular blockade. A case report |journal=British Journal of Anaesthesia |volume=44 |issue=12 |pages=1329–32 |doi=10.1093/bja/44.12.1329 |pmid=4568132|doi-access=free }}</ref> The aminoglycoside [[tobramycin]] has not been reported to exacerbate myasthenia gravis and may be used in people that require aminoglycoside treatment.<ref name="pmid33917535" /> Because of the rarity or absent reports on their exacerbation of myasthenia gravis, the following antibiotics are considered safe to use in people with myasthenia gravis: the [[cephalosporin]] class of drugs, [[sulfa drug]]s, the [[Tetracycline antibiotics|tetracycline group of drugs]], [[clindamycin]], [[polymyxin B]], and [[nitrofurantoin]].<ref name="pmid33917535" />

[[Checkpoint inhibitor|Immune checkpoint inhibitors]]: Immune checkpoint inhibitors promote certain types of autoimmune responses by blocking checkpoint pathways that inhibit these responses. They are used to treat cancers that promote their own growth and spread by stimulating checkpoint pathways. These checkpoint inhibitors include [[pembrolizumab]], [[nivolumab]], [[ipilimumab]], [[avelumab]], [[atezolizumab]], and [[durvalumab]]. From a total 5,898 people who received these drugs, 52 developed new onset myasthenia gravis and 11 had a flare of their preexisting myasthenia gravis. The symptoms of myasthenia gravis developed within 6 days to 16 weeks (median time 4 weeks). Their medicine-induced myasthenia gravis symptoms were often severe with 29 people developing [[respiratory failure]] that required [[mechanical ventilation]].<ref name="pmid31753014">{{Cite journal |vauthors=Safa H, Johnson DH, Trinh VA, Rodgers TE, Lin H, Suarez-Almazor ME, Fa'ak F, Saberian C, Yee C, Davies MA, Tummala S, Woodman K, Abdel-Wahab N, Diab A |date=November 2019 |title=Immune checkpoint inhibitor related myasthenia gravis: single center experience and systematic review of the literature |journal=Journal for Immunotherapy of Cancer |volume=7 |issue=1 |article-number=319 |doi=10.1186/s40425-019-0774-y |pmc=6868691 |pmid=31753014 |doi-access=free}}</ref> Other studies have reported that these checkpoint inhibitors cause respiratory failure in 45% and death in 25–40% of people with myasthenia gravis.<ref name="pmid33917535" /><ref name="pmid30638612">{{Cite journal |vauthors=Puwanant A, Isfort M, Lacomis D, Živković SA |date=February 2019 |title=Clinical spectrum of neuromuscular complications after immune checkpoint inhibition |journal=Neuromuscular Disorders |volume=29 |issue=2 |pages=127–133 |doi=10.1016/j.nmd.2018.11.012 |pmid=30638612}}</ref>

[[Statin]]s: Statins are drugs that lower blood [[cholesterol]] levels in order to reduce the risk of developing a [[cardiovascular disease]] due to [[atherosclerosis]]. In a 2019 review of 169 people who were reported to develop myasthenia gravis or had worsened myasthenia gravis symptoms while taking a statin, 138 had developed generalized myasthenia gravis, 13 had developed ocular myasthenia gravis, and 18 had worsening of their myasthenia gravis. Following discontinuance of the statin and treatment of their myasthenia gravis, 63 people fully recovered, 27 people were recovering, 19 people had not yet recovered, 5 people recovered but had ongoing symptoms, 1 individual had died, and there was no follow-up data for 54 people. Among these cases, 56% were considered to be serious.<ref name="pmid31298743">{{Cite journal |vauthors=Gras-Champel V, Batteux B, Masmoudi K, Liabeuf S |date=October 2019 |title=Statin-induced myasthenia: A disproportionality analysis of the WHO's VigiBase pharmacovigilance database |journal=Muscle & Nerve |volume=60 |issue=4 |pages=382–386 |doi=10.1002/mus.26637 |pmid=31298743}}</ref> A 2024 study evaluated 593 people who had myasthenia gravis and 790,399 people who did not have myasthenia gravis after being treated with a statin. The statin-treatment caused small but statistically significant increases in numbers of exacerbations of myasthenia gravis as well as new onsets of myasthenia gravis in people without the disorder. The development of myasthenia gravis in people without myasthenia gravis appeared to be more likely in people over 60 years of age.<ref name="pmid39609410">{{cite journal | vauthors = Xu W, Yan VK, Zhang Z, Fung KK, Chan KH, Lau KK, Chui CS, Lai FT, Li X, Chan EW, Wong IC, Wan EY | title = Myasthenia gravis following statin therapy: evidence from target trial emulation and self-controlled case series study | journal = Nature Communications | volume = 15 | issue = 1 | article-number = 10317 | date = November 2024 | pmid = 39609410 | pmc = 11604770 | doi = 10.1038/s41467-024-54097-1 | bibcode = 2024NatCo..1510317X }}</ref> Six non-statin cholesterol-lowering drugs, [[nicotinic acid]], [[cholestyramine]], [[colestipol]], [[colesevelam]], [[alirocumab]], and [[evolocumab]], have been used in people without causing or worsening myasthenia gravis.<ref name="pmid33917535" />

[[Adrenergic receptor#Beta blockers|Beta blockers]]: Beta blockers (i.e., β-blockers) are drugs that block the binding of two [[stress hormones]], [[epinephrine]] and [[norepinephrine]], to their target [[Adrenergic receptor#β receptors|beta receptors]]. They are used to decrease the heart rate, reduce the force of heart contractions, and relax blood vessels in order to lower [[blood pressure]] and reduce the workload on the heart. In one study the odds of an myasthenia gravis exacerbation after taking a beta blocker was increased 2.7-fold compared with people with myasthenia gravis not taking a beta blocker. These exacerbations generally did not occur immediately after their usage and therefore may have reflected other comorbidities in people with myasthenia gravis being treated with beta blockers.<ref name="pmid31469909">{{cite journal | vauthors = Gummi RR, Kukulka NA, Deroche CB, Govindarajan R | title = Factors associated with acute exacerbations of myasthenia gravis | journal = Muscle & Nerve | volume = 60 | issue = 6 | pages = 693–699 | date = December 2019 | pmid = 31469909 | doi = 10.1002/mus.26689 | url = }}</ref><ref name="pmid36373673">{{cite journal | vauthors = Marriott M, Schwery A, VandenBerg A | title = Myasthenia gravis: What does a pharmacist need to know? | journal = American Journal of Health-System Pharmacy | volume = 80 | issue = 5 | pages = 249–257 | date = February 2023 | pmid = 36373673 | doi = 10.1093/ajhp/zxac343 | url = }}</ref> In a study of 20 people with myasthenia gravis treated with a beta blocker, 3 who received oral [[metoprolol]], 9 who received intravenous metoprolol, 1 who received oral [[labetalol]], and 9 who received intravenous labetalol, only one (i.e., 5%) of the 20 participants (who received intravenous labetalol) reacted with an exacerbation of myasthenia gravis symptoms.<ref name="pmid">{{cite journal | vauthors = Petrucelli N, Barra ME, Koehl JL | title = Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis | journal = The Neurohospitalist | volume = 14 | issue = 1 | pages = 52–57 | date = January 2024 | pmid = 38235027| pmc = 10790617 | doi = 10.1177/19418744231206256 | url = }}</ref>

[[Antiarrhythmic agents|Ia antiarrhythmic agents]]: A type Ia antiarrhythmic agent (see [[Antiarrhythmic agent#Vaughan Williams classification|Vaughan Williams classification]]), i.e., [[procainamide]], which is used to treat [[cardiac arrhythmia]]s, has caused [[respiratory failure]] in people with myasthenia gravis who, prior to being treated with it, did not have respiratory symptoms. Furthermore, this drug has caused MG-like symptoms in people who have kidney failure but do not have myasthenia gravis. And, procainamide worsened muscle dysfunction in a rat model of human myasthenia gravis.<ref name="pmid33917535" />

[[Neuromuscular-blocking drug#Depolarizing blocking agents|Depolarizing neuromuscular blockers]]: Depolarizing neuromuscular blockers suppress the neurons' signaling at neuromuscular junctions thereby reducing the affected skeletal muscles contractibility. These blockers are used as muscle relaxants in people undergoing surgery.<ref name="pmid35322378">{{Cite journal |vauthors=van den Bersselaar LR, Gubbels M, Riazi S, Heytens L, Jungbluth H, Voermans NC, Snoeck MM |date=June 2022 |title=Mapping the current evidence on the anesthetic management of adult patients with neuromuscular disorders-a scoping review |journal=Canadian Journal of Anaesthesia |volume=69 |issue=6 |pages=756–773 |doi=10.1007/s12630-022-02230-3 |pmc=9132812 |pmid=35322378}}</ref> [[Succinylcholine]] is the only depolarizing neuromuscular blocker available in the US market.<ref name="pmid33917535" /> Succinylcholine's ability to induce or worsen myasthenia gravis is unclear. It has been suggested to cause life-threatening side effects such as [[rhabdomyolysis]], [[myotonia]], and [[hyperkalemia]] in people with muscle disease although the role of succinylcholine in causing these side effects also remains unclear.<ref name="pmid35322378" /><ref name="pmid33917535" />

[[Inhalation anesthetics]]: Inhalation anesthetics are [[general anesthetic]]s that are delivered by inhalation generally for people undergoing surgery. People with myasthenia gravis undergoing surgery with inhaled anesthetics (i.e., [[halothane]], [[isoflurane]], [[enflurane]], and [[sevoflurane]]) may develop neuromuscular blockage and have an increased incidence of developing a life-threatening myasthenia crisis which must be treated by prolonged mechanical ventilation. In a study of 795 people with myasthenia gravis undergoing surgical removal of their thymus under general anesthesia, [[sugammadex]], a [[neuromuscular-blocking drug]] (i.e., a drug that reverses neuromuscular blockade) significantly reduced the development of this crisis.<ref name="pmid33917535" /><ref name="pmid31124838">{{Cite journal |vauthors=Mouri H, Jo T, Matsui H, Fushimi K, Yasunaga H |date=February 2020 |title=Effect of Sugammadex on Postoperative Myasthenic Crisis in Myasthenia Gravis Patients: Propensity Score Analysis of a Japanese Nationwide Database |journal=Anesthesia and Analgesia |volume=130 |issue=2 |pages=367–373 |doi=10.1213/ANE.0000000000004239 |pmid=31124838}}</ref>

[[Glucocorticoids]]: Glucocorticoids are anti-inflammatory agents that in initial studies were used at high dosages and found to worsen myasthenia gravis in 25-75% of cases.<ref name="pmid25069701">{{Cite journal |vauthors=Hoffmann S, Kohler S, Ziegler A, Meisel A |date=October 2014 |title=Glucocorticoids in myasthenia gravis - if, when, how, and how much? |journal=Acta Neurologica Scandinavica |volume=130 |issue=4 |pages=211–21 |doi=10.1111/ane.12261 |pmid=25069701 |doi-access=free}}</ref> However, further studies found that glucocorticoids do have favorable effects on myasthenia gravis when taken long term. Two glucocorticoids, oral [[prednisone]] and [[prednisolone]], are the first-line [[immunosuppressive]] treatment for myasthenia gravis.<ref name="pmid33917535" /><ref name="pmid35350948">{{Cite journal |vauthors=Dalakas MC, Meisel A |date=April 2022 |title=Immunomodulatory effects and clinical benefits of intravenous immunoglobulin in myasthenia gravis |journal=Expert Review of Neurotherapeutics |volume=22 |issue=4 |pages=313–318 |doi=10.1080/14737175.2022.2057223 |pmid=35350948 |doi-access=free}}</ref><ref name="pmid38306763">{{Cite journal |vauthors=Ghimire A, Kunwar B, Aryal B, Gaire A, Bist A, Shah B, Mainali A, Ghimire B, Gajurel BP |date=March 2024 |title=Assessing the comparative efficacy of plasmapheresis and Intravenous immunoglobulin in myasthenia gravis treatment: A systematic review and meta-analysis |journal=Journal of Clinical Neuroscience |volume=121 |pages=1–10 |doi=10.1016/j.jocn.2024.01.025 |pmid=38306763}}</ref> A review published in 2020 on 27 earlier publications found that myasthenia gravis was worsened by glucocorticoids in 33.3% of patients. These myasthenia gravis exacerbations seemed significantly greater for [[cortisone]], intermediate for prednisone, and lowest for methylprednisolone. High dosages or alternate day dosages of prednisone were associated with exacerbation more frequently than low-dose treatments. Most of these exacerbations were mild to moderately severe and developed more often in patients who were older in age or had generalized myasthenia gravis, myasthenia gravis with bulbar symptoms, severe symptoms, a thymoma, or a history of thymectomy to remove a thymoma. These studies, however, were mostly of low quality. Prospective studies comparing the effects of the different corticosteroids and corticosteroids to define the rate and severity of the myasthenia exacerbations are needed.<ref name="pmid33064188">{{cite journal | vauthors = Lotan I, Hellmann MA, Wilf-Yarkoni A, Steiner I | title = Exacerbation of myasthenia gravis following corticosteroid treatment: what is the evidence? A systematic review | journal = Journal of Neurology | volume = 268 | issue = 12 | pages = 4573–4586 | date = December 2021 | pmid = 33064188 | doi = 10.1007/s00415-020-10264-0 | url = }}</ref>

[[Calcium channel blocker]]s: Calcium channel blockers (e.g., [[felodipine]], [[nifedipine]], and [[verapamil]]) are drugs that lower [[blood pressure]] in people with [[hypertension]]. Felodipine and nifedipine are reported to worsen myasthenia gravis and nifedipine and verapamil are reported to cause respiratory failure in people with severe generalized myasthenia gravis.<ref name="pmid33917535" />

[[Penicillamine]]: Penicillamine is a [[chelation therapy]] drug used to treat various diseases (e.g., [[Wilson's disease]]). About 1-2% of individuals treated long term with penicillamine develop myasthenia gravis and/or develop low concentrations of antibodies to AChR.<ref name="pmid11445126">{{Cite journal |vauthors=Vincent A, Palace J, Hilton-Jones D |date=June 2001 |title=Myasthenia gravis |journal=Lancet |volume=357 |issue=9274 |pages=2122–8 |doi=10.1016/S0140-6736(00)05186-2 |pmid=11445126}}</ref> Their myasthenia gravis is often mild and predominantly ocular myasthenia gravis, becomes evident usually 6–7 months (range one month to 8 years) after starting the drug, and goes into complete remission in 70% of the cases within 6–10 months after discontinuing the drug.<ref name="pmid33917535" />

[[Botulinum toxin|Botulinum toxin A]]: Botulinum toxin A (sold under the brand name Botox, Jeuveau, and Xeomin) blocks transmission at [[neuromuscular junction]]s to paralyze the muscles into which it is injected. Local botulinum toxin A injections for cosmetic purposes have on occasion caused weaknesses in distant muscles, symptoms resembling ocular or generalized myasthenia gravis in individuals with subclinical myasthenia gravis, and exacerbations of previously controlled myasthenia gravis. Botulinum toxin A has also been used to treat [[spasmodic torticollis]] (i.e., involuntarily neck turning), [[blepharospasm]] (involuntary contraction of the eye lids), and other uncontrolled facial muscle spasms in people with myasthenia gravis without side effects or with only short-lived [[dysphagia]] or [[diplopia]].<ref name="pmid33917535" />

[[Magnesium]]: Magnesium is a [[chemical element]] that blocks skeletal muscle contraction by inhibiting the release or [[acetylcholine]] at the neuromuscular junction and also by lowering the sensitivity of these muscles to acetylcholine.<ref name="pmid33917535" /> Respiratory failure has occurred after systemic use of magnesium (mainly in the form of intravenous [[magnesium sulfate]] injections) for [[pre-eclampsia]] and after magnesium replacement during the course of a hospitalization in people with underlying myasthenia gravis.<ref name="pmid33917535" /><ref name="pmid38235027">{{Cite journal |vauthors=Petrucelli N, Barra ME, Koehl JL |date=January 2024 |title=Evaluation of Medication Exposure on Exacerbation of Disease in Patients With Myasthenia Gravis |journal=The Neurohospitalist |volume=14 |issue=1 |pages=52–57 |doi=10.1177/19418744231206256 |pmc=10790617 |pmid=38235027 }}</ref>

[[Local anesthetics]]: Local anesthetics cause absence of pain and all other sensations in a specific body part without loss of consciousness. There are two broad classes of these anesthetics: esters (i.e., [[procaine]], [[cocaine]], [[tetracaine]] [[benzocaine]], and [[chloroprocaine]]) and amides (i.e. [[lidocaine]], [[bupivacaine]], [[etidocaine]], [[levobupivacaine]], [[mepivacaine]], [[prilocaine]], and [[ropivacaine]]). Ester local anesthetics are metabolized by [[pseudocholinesterase]]s which in people with myasthenia gravis taking anticholinesterase drugs may lead to excessive levels of these ester anesthetics. Amide local anesthetics are not metabolized by psuedocholineesterases. Based on these considerations, amide local anesthetics are strongly preferred over ester local anesthetics in people with myasthenia gravis.<ref name="pmid29980408">{{Cite journal |vauthors=Muckler VC, O'Brien JM, Matson SE, Rice AN |date=February 2019 |title=Perianesthetic Implications and Considerations for Myasthenia Gravis |journal=Journal of PeriAnesthesia Nursing |volume=34 |issue=1 |pages=4–15 |doi=10.1016/j.jopan.2018.03.009 |pmid=29980408}}</ref><ref name="pmid30859135">{{Cite journal |vauthors=Prabhu SS, Khan SA, Doudnikoff AL, Reebye UN |date=February 2019 |title=Anesthetic considerations for a patient with myasthenia gravis undergoing deep sedation in an outpatient oral surgery setting |journal=Journal of Dental Anesthesia and Pain Medicine |volume=19 |issue=1 |pages=67–72 |doi=10.17245/jdapm.2019.19.1.67 |pmc=6405345 |pmid=30859135}}</ref>

Other Drugs: Rare cases of myasthenia gravis exacerbations have been reported in people treated with: '''1)''' [[penicillins]], i.e., [[ampicillin]] and [[amoxicillin]]; '''2)''' anti-cancer medications, i.e., [[lorlatinib]], [[nilotinib]], [[imatinib]] (these three drugs are [[tyrosine kinase inhibitor]]s that may also cause myasthenia gravis), [[dabrafenib]], and [[trametinib]]; '''3)''' [[antipsychotic]] drugs, i.e., [[chlorpromazine]], [[pimozide]], [[thioridazine]], [[clozapine]], [[olanzapine]], [[haloperidol]], [[quetiapine]], [[risperidone]], and [[olanzapine]]; '''4)''' [[Interferon type 1#IFN-α|IFN-α]] (may also cause myasthenia gravis); and '''5)''' the chemical element, [[lithium]]. These agents can be used in people with myasthenia gravis because reports on their exacerbation (or induction) of myasthenia gravis are rare.<ref name="pmid33917535" />

==Pathophysiology==
Myasthenia gravis is an [[autoimmune]] [[synaptopathy]]. The disorder occurs when the immune system malfunctions and generates antibodies that attack the body's tissues. The antibodies in MG attack a normal human protein, the nicotinic acetylcholine receptor, or a related protein called [[MuSK protein|MuSK]], a muscle-specific kinase.<ref>{{Cite journal |vauthors=Valenzuela DM, Stitt TN, DiStefano PS, Rojas E, Mattsson K, Compton DL, Nunez L, Park JS, Stark JL, Gies DR, Thomas S, LeBeau MM, Fernald AA, Copeland NG, Jenkins NA, Burden SJ, Glass DJ, Yancopoulos GD |date=Sep 1995 |title=Receptor tyrosine kinase specific for the skeletal muscle lineage: expression in embryonic muscle, at the neuromuscular junction, and after injury |journal=Neuron |volume=15 |issue=3 |pages=573–584 |doi=10.1016/0896-6273(95)90146-9 |pmid=7546737 |doi-access=free }}</ref><ref>{{Cite web |title=Myasthenia gravis |url=https://medlineplus.gov/genetics/condition/myasthenia-gravis/ |url-status=live |archive-url=https://web.archive.org/web/20150711123926/http://ghr.nlm.nih.gov/condition/myasthenia-gravis |archive-date=11 July 2015 |access-date=2015-07-10 |website=Genetics Home Reference}}</ref> Other, less frequent antibodies are found against [[low-density lipoprotein receptor-related protein 4|LRP4]], [[agrin]], and [[titin]] proteins.<ref name="Pathogenesis of myasthenia gravis" /><ref>{{Cite journal |vauthors=Sinmaz N, Nguyen T, Tea F, Dale RC, Brilot F |date=August 2016 |title=Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system |journal=Journal of Neuroinflammation |volume=13 |issue=1 |article-number=219 |doi=10.1186/s12974-016-0678-4 |pmc=5006540 |pmid=27577085 |doi-access=free}}</ref>

[[Human leukocyte antigen]] haplotypes are associated with increased susceptibility to myasthenia gravis and other autoimmune disorders. Relatives of people with myasthenia gravis have a higher percentage of other immune disorders.<ref>{{Cite journal |vauthors=Sathasivam S |date=January 2014 |title=Diagnosis and management of myasthenia gravis |journal=Progress in Neurology and Psychiatry |volume=18 |issue=1 |pages=6–14 |doi=10.1002/pnp.315 |doi-access=free }}</ref><ref>{{Cite web |title=Myasthenia Gravis |url=https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024823/ |archive-url=https://web.archive.org/web/20161018194009/https://www.ncbi.nlm.nih.gov/pubmedhealth/PMHT0024823/ |archive-date=18 October 2016 |access-date=2015-07-09 |website=PubMed Health |publisher=U.S. National Library of Medicine |location=Bethesda, MD |author1=Pmhdev }}</ref>

The thymus gland cells form part of the body's immune system. In those with myasthenia gravis, the thymus gland is large and abnormal. It sometimes contains clusters of immune cells that indicate lymphoid hyperplasia, and the thymus gland may give wrong instructions to immune cells.<ref>{{Cite web |title=Myasthenia Gravis Fact Sheet |url=http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm |archive-url=https://web.archive.org/web/20150711193029/http://www.ninds.nih.gov/disorders/myasthenia_gravis/detail_myasthenia_gravis.htm |archive-date=11 July 2015 |access-date=2015-07-10 |website=www.ninds.nih.gov |publisher=National Institute of Neurological Disorders and Stroke (NINDS)}}</ref>

<gallery widths="220px" heights="220px">
File:Synapse diag4.png|Neuromuscular junction: 1. [[Axon]] 2. Muscle cell membrane 3. [[Synaptic vesicle]] 4. [[Nicotinic acetylcholine receptor]] 5. [[Mitochondrion]]
File:Gray1178.png|A juvenile thymus shrinks with age.
File:Nicotinic Acetylcholine receptor.png|The [[nicotinic acetylcholine receptor]]
</gallery>

===In pregnancy===
For women who are pregnant and already have MG, in a third of cases, they have been known to experience an exacerbation of their symptoms, and in those cases, it usually occurs in the [[first trimester]] of pregnancy.<ref name=":4">{{Cite journal |vauthors=Varner M |date=June 2013 |title=Myasthenia gravis and pregnancy |journal=Clinical Obstetrics and Gynecology |volume=56 |issue=2 |pages=372–81 |doi=10.1097/GRF.0b013e31828e92c0 |pmid=23563874}}</ref> Signs and symptoms in pregnant mothers tend to improve during the [[second trimester|second]] and [[third trimester]]s. Complete [[remission (medicine)|remission]] can occur in some mothers.<ref name="tellez">{{Cite journal |vauthors=Téllez-Zenteno JF, Hernández-Ronquillo L, Salinas V, Estanol B, da Silva O |date=November 2004 |title=Myasthenia gravis and pregnancy: clinical implications and neonatal outcome |journal=BMC Musculoskeletal Disorders |volume=5 |issue=1 |article-number=42 |doi=10.1186/1471-2474-5-42 |pmc=534111 |pmid=15546494 |doi-access=free}}</ref> [[Immunosuppressive therapy]] should be maintained throughout pregnancy, as this reduces the chance of neonatal muscle weakness, and controls the mother's myasthenia.<ref name="OTM3" />

About 10–20% of infants with mothers affected by the condition are born with transient neonatal myasthenia gravis (TNMG), which generally produces feeding and [[Respiratory system|respiratory]] difficulties that develop about 12 hours to several days after birth.<ref name=":4" /><ref name="OTM3">{{Cite book |title=Oxford Textbook of Medicine |vauthors=Warrell DA, Cox TM |publisher=Oxford |year=2003 |isbn=978-0-19-852787-9 |edition=Fourth |volume=3 |page=1170 |display-authors=etal}}</ref> A child with TNMG typically responds very well to acetylcholinesterase inhibitors, and the condition generally resolves over a period of three weeks, as the antibodies diminish, and generally does not result in any complications.<ref name=":4" /> However, a small percentage of fetuses and newborns with TNMG, particularly those who have antibodies directed against the fetal form of the AChR (their disorder is a subtype of TNMG termed the "acetylcholine receptor inactivation syndrome") have a more severe form of TNMG which includes weakness in skeletal muscles regulating breathing, respiratory failure, and various deformities such as [[arthrogryposis multiplex congenita]]. In some of these cases, the mother remains [[asymptomatic]].<ref name="OTM3" /><ref name="pmid37186601">{{Cite journal |vauthors=Allen NM, O'Rahelly M, Eymard B, Chouchane M, Hahn A, Kearns G, Kim DS, Byun SY, Nguyen CE, Schara-Schmidt U, Kölbel H, Marina AD, Schneider-Gold C, Roefke K, Thieme A, Van den Bergh P, Avalos G, Álvarez-Velasco R, Natera-de Benito D, Cheng MH, Chan WK, Wan HS, Thomas MA, Borch L, Lauzon J, Kornblum C, Reimann J, Mueller A, Kuntzer T, Norwood F, Ramdas S, Jacobson LW, Jie X, Fernandez-Garcia MA, Wraige E, Lim M, Lin JP, Claeys KG, Aktas S, Oskoui M, Hacohen Y, Masud A, Leite MI, Palace J, De Vivo D, Vincent A, Jungbluth H |date=October 2023 |title=The emerging spectrum of fetal acetylcholine receptor antibody-related disorders (FARAD) |journal=Brain: A Journal of Neurology |volume=146 |issue=10 |pages=4233–4246 |doi=10.1093/brain/awad153 |pmc=10545502 |pmid=37186601}}</ref>

==Diagnosis==
Myasthenia gravis can be difficult to diagnose, as the symptoms can be subtle and hard to distinguish from both normal variants and other neurological disorders.<ref name="Scherer2005" />

Three types of myasthenic symptoms in children can be distinguished:<ref>{{Cite book |url=https://books.google.com/books?id=tlGAAgAAQBAJ&pg=PA277 |title=Pediatric Nursing: The Critical Components of Nursing Care |vauthors=Rudd K, Kocisko D |publisher=F.A. Davis |year=2013 |isbn=978-0-8036-4053-5 |archive-url=https://web.archive.org/web/20160603224352/https://books.google.com/books?id=tlGAAgAAQBAJ&pg=PA277 |archive-date=3 June 2016 |url-status=live}}</ref>
# Transient neonatal myasthenia gravis occurs in 10 to 15% of babies born to mothers afflicted with the disorder, and disappears after a few weeks.
# Congenital myasthenia, the rarest form, occurs when genes are present from both parents.
# Juvenile myasthenia gravis is most common in females.

Congenital myasthenias cause muscle weakness and fatigability similar to those of MG.<ref name="EngelShen2015">{{Cite journal |vauthors=Engel AG, Shen XM, Selcen D, Sine SM |date=April 2015 |title=Congenital myasthenic syndromes: pathogenesis, diagnosis, and treatment |journal=The Lancet. Neurology |volume=14 |issue=4 |pages=420–434 |doi=10.1016/S1474-4422(14)70201-7 |pmc=4520251 |pmid=25792100}}</ref>
The signs of congenital myasthenia usually are present in the first years of childhood, although they may not be recognized until adulthood.<ref>{{Cite web |title=Congenital Myasthenia Information Page: National Institute of Neurological Disorders and Stroke (NINDS) |url=http://www.ninds.nih.gov/disorders/congenital_myasthenia/congenital_myasthenia.htm |archive-url=https://web.archive.org/web/20150712234330/http://www.ninds.nih.gov/disorders/congenital_myasthenia/congenital_myasthenia.htm |archive-date=12 July 2015 |access-date=2015-07-11 |website=www.ninds.nih.gov}}</ref>

=== Subgroup classification ===
{| class="wikitable" style = "float: right; margin-left:15px; text-align:center"
|+ '''Myasthenia Gravis Foundation of America Clinical Classification'''<ref>{{Cite book |title=Myasthenia Gravis and Related Disorders |vauthors=Wolfe GI, Barohn RJ |year=2009 |isbn=978-1-58829-852-2 |pages=293–302 |chapter=Myasthenia Gravis: Classification and Outcome Measurements |doi=10.1007/978-1-59745-156-7_18}}</ref>
|-
! Class !! Description
|-
| I || Any eye muscle weakness, possible [[ptosis (eyelid)|ptosis]], no other evidence of muscle weakness elsewhere
|-
| II || Eye muscle weakness of any severity, mild weakness of other muscles
|-
| IIa || Predominantly limb or axial muscles
|-
| IIb || Predominantly bulbar and/or respiratory muscles
|-
| III || Eye muscle weakness of any severity, moderate weakness of other muscles
|-
| IIIa || Predominantly limb or axial muscles
|-
| IIIb || Predominantly bulbar and/or respiratory muscles
|-
| IV || Eye muscle weakness of any severity, severe weakness of other muscles
|-
| IVa || Predominantly limb or axial muscles
|-
| IVb || Predominantly bulbar and/or respiratory muscles
|-
| V || Intubation needed to maintain airway
|}
When diagnosed with myasthenia gravis, an individual can be stratified into distinct subgroups based on the clinical features and serological status, e.g. affected muscle group, age of onset, thymic abnormalities, and profile of serum autoantibodies.<ref>{{Cite journal |last1=Meriggioli |first1=Matthew N |last2=Sanders |first2=Donald B |date=May 2009 |title=Autoimmune myasthenia gravis: emerging clinical and biological heterogeneity |journal=The Lancet Neurology |volume=8 |issue=5 |pages=475–490 |doi=10.1016/S1474-4422(09)70063-8 |pmc=2730933 |pmid=19375665}}</ref>

Based on the affected muscle group, people with myasthenia gravis can be sub-grouped into ocular myasthenia gravis or generalized myasthenia gravis. Ocular myasthenia gravis is characterized by exclusively ocular symptoms, droopy eyelids, or double vision. Generalized myasthenia gravis has muscle weakness with a variable combination of the bulbar, axial, or limb and respiratory muscles.<ref>{{Cite journal |last1=Gilhus |first1=Nils Erik |last2=Verschuuren |first2=Jan J |date=October 2015 |title=Myasthenia gravis: subgroup classification and therapeutic strategies |journal=The Lancet Neurology |volume=14 |issue=10 |pages=1023–1036 |doi=10.1016/s1474-4422(15)00145-3 |pmid=26376969 }}</ref>

People with myasthenia gravis can also be sub-grouped by the age of onset: juvenile-onset myasthenia gravis (onset age ≤ 18 years of age), early-onset MG (EOMG; 19–50 years of age), late-onset MG (LOMG; onset > 50 years of age), and very late-onset (VLOMG; onset age ≥ 65 years of age).<ref>{{Cite journal |last1=Punga |first1=Anna Rostedt |last2=Maddison |first2=Paul |last3=Heckmann |first3=Jeannine M |last4=Guptill |first4=Jeffrey T |last5=Evoli |first5=Amelia |date=February 2022 |title=Epidemiology, diagnostics, and biomarkers of autoimmune neuromuscular junction disorders |url=https://linkinghub.elsevier.com/retrieve/pii/S1474442221002970 |journal=The Lancet Neurology |volume=21 |issue=2 |pages=176–188 |doi=10.1016/S1474-4422(21)00297-0 |pmid=35065040|url-access=subscription }}</ref>

The subgroup of the autoantibody profile includes AChR seropositive, MuSK seropositive, LRP4 seropositive, and agrin seropositive.<ref>{{cite journal |last1=Koneczny |first1=Inga |last2=Herbst |first2=Ruth |title=Myasthenia Gravis: Pathogenic Effects of Autoantibodies on Neuromuscular Architecture |journal=Cells |date=2 July 2019 |volume=8 |issue=7 |page=671 |doi=10.3390/cells8070671 |pmc=6678492 |pmid=31269763 |doi-access=free}}</ref>

===Physical examination===
During a physical examination to check for MG, a doctor might ask the person to perform repetitive movements. For instance, the doctor may ask one to look at a fixed point for 30 seconds and to relax the muscles of the forehead, because a person with MG and ptosis of the eyes might be involuntarily using the forehead muscles to compensate for the weakness in the eyelids.<ref name="Scherer2005" /> The clinical examiner might also try to elicit the "curtain sign" in a person by holding one of the person's eyes open, which in the case of MG will lead the other eye to close.<ref name="Scherer2005" />

=== Train of four ratio test ===
The train of four ratio (i.e., ToFr) is a [[Neuromuscular monitoring|neuromuscular test]] for monitoring neuromuscular function (see [[Postoperative residual curarization#Monitoring neuromuscular blockade|monitoring neuromuscular blockade]]). In this test, a [[Peripheral nervous system|peripheral nerve]] (most commonly the [[ulnar nerve]]) is stimulated by an electrical impulse 4 times (i.e., T1, T2, T3, T4) and the strength of contraction is measured in a muscle(s) (i.e., the [[Abductor pollicis longus muscle|abductor pollicis longus]] and [[Abductor pollicis brevis muscle|brevis muscles]] for the ulnar nerve). The ratio of the amplitude of muscle contraction in response to the fourth impulse (T4) divided by the amplitude of muscle contraction in response to the first impulse is calculated. The ratio of these two contractions should be 1.0. Values less that this are regarded as abnormal.<ref name="pmid29365307">{{cite journal | vauthors = Ortega R, Brull SJ, Prielipp R, Gutierrez A, De La Cruz R, Conley CM | title = Monitoring Neuromuscular Function | journal = The New England Journal of Medicine | volume = 378 | issue = 4 | pages = e6 | date = January 2018 | pmid = 29365307 | doi = 10.1056/NEJMvcm1603741 | url = }}</ref> ToFr is used to determine when the effects of an administered [[neuromuscular-blocking drug]] have worn off (see [[postoperative residual curarization]])<ref name="pmid29365307"/> or as the most objective, accurate, and sensitive test for determining the presence and severity of myasthenia gravis: myasthenia gravis is considered to afflict the tested muscle if its ToFr ratio (i.e., T4/T1) is less than 0.9.<ref name="pmid10910480">{{cite journal | vauthors = Mann R, Blobner M, Jelen-Esselborn S, Busley R, Werner C | title = Preanesthetic train-of-four fade predicts the atracurium requirement of myasthenia gravis patients | journal = Anesthesiology | volume = 93 | issue = 2 | pages = 346–50 | date = August 2000 | pmid = 10910480 | doi = 10.1097/00000542-200008000-00011 | url = }}</ref>

===Blood tests===
If the diagnosis is suspected, [[serology]] can be performed:
* One test is for antibodies against the acetylcholine receptor;<ref name="Scherer2005" /> the test has a reasonable [[Sensitivity (tests)|sensitivity]] of 80–96%, but in ocular myasthenia, the sensitivity falls to 50%.
* A proportion of the people without antibodies against the acetylcholine receptor have antibodies against the MuSK protein.<ref name="pmid18515870">{{Cite journal |display-authors=6 |vauthors=Leite MI, Jacob S, Viegas S, Cossins J, Clover L, Morgan BP, Beeson D, Willcox N, Vincent A |date=July 2008 |title=IgG1 antibodies to acetylcholine receptors in 'seronegative' myasthenia gravis |journal=Brain |volume=131 |issue=Pt 7 |pages=1940–52 |doi=10.1093/brain/awn092 |pmc=2442426 |pmid=18515870}}</ref>
* Less than 1% of patients with myasthenia gravis have antibodies against [[low-density lipoprotein receptor-related protein 4]] (i.e., LRP4).<ref name="pmid38494283">{{cite journal | vauthors = Tannemaat MR, Huijbers MG, Verschuuren JJ | title = Myasthenia gravis-Pathophysiology, diagnosis, and treatment | journal = Handbook of Clinical Neurology | volume = 200 | issue = | pages = 283–305 | date = 2024 | pmid = 38494283 | doi = 10.1016/B978-0-12-823912-4.00026-8 | url = }}</ref>
* In specific situations, testing is performed for [[Lambert-Eaton syndrome]].<ref>{{MedlinePlusEncyclopedia|000710|Lambert-Eaton syndrome}}</ref>

===Electrodiagnostics===
[[File:Tumor Thymoma1.JPG|thumb|A chest CT-scan showing a thymoma (red circle)]]
[[File:Myasthenia gravis ptosis reversal.jpg|thumb|Photograph of a person showing right partial ptosis (left picture), the left lid shows compensatory pseudo lid retraction because of equal innervation of the m. levator palpabrae superioris ([[Hering's law of equal innervation]]): Right picture: after an edrophonium test, note the improvement in ptosis.]]

Muscle fibers of people with MG are easily fatigued, which the [[repetitive nerve stimulation]] test can help diagnose. In single-fiber [[electromyography]], which is considered to be the most sensitive (although not the most specific) test for MG,<ref name="Scherer2005" /> a thin needle electrode is inserted into different areas of a particular muscle to record the action potentials from several samplings of different individual muscle fibers. Two muscle fibers belonging to the same motor unit are identified, and the temporal variability in their firing patterns is measured. Frequency and proportion of particular abnormal action potential patterns, called "jitter" and "blocking", are diagnostic. Jitter refers to the abnormal variation in the time interval between action potentials of adjacent muscle fibers in the same motor unit. Blocking refers to the failure of nerve impulses to elicit action potentials in adjacent muscle fibers of the same motor unit.<ref name="Selvan">{{Cite journal |vauthors=Selvan VA |date=January 2011 |title=Single-fiber EMG: A review |journal=Annals of Indian Academy of Neurology |volume=14 |issue=1 |pages=64–67 |doi=10.4103/0972-2327.78058 |pmc=3108086 |pmid=21654930 |doi-access=free}}</ref>

===Ice test===
Applying ice for 2–5 minutes to the muscles reportedly has a [[sensitivity and specificity]] of 76.9% and 98.3%, respectively, for the identification of MG. [[Acetylcholinesterase]] is thought to be inhibited at the lower temperature, which is the basis for this diagnostic test. This generally is performed on the eyelids when ptosis is present and is deemed positive if a ≥2-mm rise in the eyelid occurs after the ice is removed.<ref>{{Cite journal |vauthors=Kearsey C, Fernando P, D'Costa D, Ferdinand P |date=June 2010 |title=The use of the ice pack test in myasthenia gravis |journal=JRSM Short Reports |volume=1 |issue=1 |page=14 |doi=10.1258/shorts.2009.090037 |pmc=2984327 |pmid=21103106}}</ref>

===Edrophonium test===
This test requires the [[intravenous]] administration of [[edrophonium|edrophonium chloride]] or neostigmine, drugs that block the breakdown of acetylcholine by [[cholinesterase]] (acetylcholinesterase inhibitors).<ref>{{MedlinePlusEncyclopedia|003930|Tensilon test}}</ref> This test is no longer typically performed, as its use can lead to life-threatening [[bradycardia]] (slow heart rate) which requires immediate emergency attention.<ref name=":2">{{Cite journal |vauthors=Spillane J, Higham E, Kullmann DM |date=December 2012 |title=Myasthenia gravis |journal=BMJ |volume=345 |issue=dec21 3 |article-number=e8497 |doi=10.1136/bmj.e8497 |pmid=23261848 }}</ref> Production of edrophonium was discontinued in 2008.<ref name="Rosen2014" />

===Imaging===
A [[chest X-ray]] may identify widening of the [[mediastinum]] suggestive of thymoma, but [[computed tomography]] or [[magnetic resonance imaging]] (MRI) are more sensitive ways to identify thymomas and are generally done for this reason.<ref name="Kraker">{{Cite journal |vauthors=de Kraker M, Kluin J, Renken N, Maat AP, Bogers AJ |date=June 2005 |title=CT and myasthenia gravis: correlation between mediastinal imaging and histopathological findings |journal=Interactive Cardiovascular and Thoracic Surgery |volume=4 |issue=3 |pages=267–271 |doi=10.1510/icvts.2004.097246 |pmid=17670406 |doi-access=free|hdl=1765/74827 |hdl-access=free }}</ref> MRI of the cranium and orbits may also be performed to exclude compressive and inflammatory lesions of the cranial nerves and ocular muscles.<ref>Allan H. Ropper, Robert H. Brown ''Adams and Victor's Principles of Neurology'' McGraw-Hill Professional; 8 edition (2005)</ref>

===Pulmonary function test===
The forced [[vital capacity]] may be monitored at intervals to detect increasing muscular weakness. Acutely, [[negative inspiratory force]] may be used to determine adequacy of ventilation; it is performed on those individuals with MG.<ref>{{MedlinePlusEncyclopedia|003853|Pulmonary function tests}}</ref><ref>{{EMedicine|article|793136|Emergent Management of Myasthenia Gravis}}</ref>

=== Differential diagnoses ===
The muscle weakness that worsens with activity (abnormal [[muscle fatigue]]) in myasthenia gravis<ref name=":0">{{cite journal |last1=Gilhus |first1=Nils Erik |title=Physical training and exercise in myasthenia gravis |journal=Neuromuscular Disorders |date=March 2021 |volume=31 |issue=3 |pages=169–173 |doi=10.1016/j.nmd.2020.12.004 |pmid=33461846 |hdl-access=free |hdl=11250/2767222 }}</ref> is a symptom shared by other neuromuscular diseases. Most of the [[Metabolic myopathy|metabolic myopathies]], such as McArdle disease (GSD-V), have abnormal muscle fatigue rather than fixed muscle weakness.<ref>{{cite journal |last1=Darras |first1=Basil T. |last2=Friedman |first2=Neil R. |title=Metabolic myopathies: a clinical approach; part I |journal=Pediatric Neurology |date=February 2000 |volume=22 |issue=2 |pages=87–97 |doi=10.1016/s0887-8994(99)00133-2 |pmid=10738913 }}</ref><ref>{{cite journal |last1=Tobon |first1=Alejandro |title=Metabolic Myopathies |journal=Continuum |date=December 2013 |volume=19 |issue=6 Muscle Disease |pages=1571–1597 |doi=10.1212/01.CON.0000440660.41675.06 |pmid=24305448 |pmc=10563931 }}</ref> Also, like myasthenia gravis,<ref name=":0" /> exercise intolerance in [[McArdle disease]] improves with regular physical activity (performed safely using activity adaptations such as getting into [[Second wind#Pathology|second wind]], the "30 for 80 rule," and "six second rule").<ref>{{Cite book |last=Wakelin |first=A. |url=https://www.iamgsd.org/_files/ugd/c951b2_91a5802caa2144d5aedbb0489c1cf543.pdf |title=Living with McArdle Disease |publisher=IamGSD |year=2017 |access-date=24 November 2023 |archive-url=https://web.archive.org/web/20230305215516/https://www.iamgsd.org/_files/ugd/c951b2_91a5802caa2144d5aedbb0489c1cf543.pdf |archive-date=5 March 2023 |url-status=live}}</ref><ref>{{Cite journal |last1=Reason |first1=S. L. |last2=Voermans |first2=N. |last3=Lucia |first3=A. |last4=Vissing |first4=J. |last5=Quinlivan |first5=R. |last6=Bhai |first6=S. |last7=Wakelin |first7=A. |date=July 2023 |title=Development of Continuum of Care for McArdle disease: A practical tool for clinicians and patients |journal=Neuromuscular Disorders |volume=33 |issue=7 |pages=575–579 |doi=10.1016/j.nmd.2023.05.006 |pmid=37354872 |doi-access=free }}</ref> A small minority of people with McArdle disease also have the comorbidity of ptosis (drooping upper eyelid).<ref>{{Cite journal |last1=Scalco |first1=Renata S. |last2=Lucia |first2=Alejandro |last3=Santalla |first3=Alfredo |last4=Martinuzzi |first4=Andrea |last5=Vavla |first5=Marinela |last6=Reni |first6=Gianluigi |last7=Toscano |first7=Antonio |last8=Musumeci |first8=Olimpia |last9=Voermans |first9=Nicol C. |last10=Kouwenberg |first10=Carlyn V. |last11=Laforêt |first11=Pascal |last12=San-Millán |first12=Beatriz |last13=Vieitez |first13=Irene |last14=Siciliano |first14=Gabriele |last15=Kühnle |first15=Enrico |date=24 November 2020 |title=Data from the European registry for patients with McArdle disease and other muscle glycogenoses (EUROMAC) |journal=Orphanet Journal of Rare Diseases |volume=15 |issue=1 |page=330 |doi=10.1186/s13023-020-01562-x |pmc=7687836 |pmid=33234167 |doi-access=free }}</ref> Late-onset GSD-II ([[Pompe disease]]) and GSD-XV also have muscle weakness or fatigue with comorbidities of ptosis and ophthalmoplegia; as do many of the [[Mitochondrial myopathy|mitochondrial myopathies]].<ref name=":3">{{Cite journal |last1=Urtizberea |first1=Jon Andoni |last2=Severa |first2=Gianmarco |last3=Malfatti |first3=Edoardo |date=May 2023 |title=Metabolic Myopathies in the Era of Next-Generation Sequencing |journal=Genes |volume=14 |issue=5 |page=954 |doi=10.3390/genes14050954 |pmc=10217901 |pmid=37239314 |doi-access=free }}</ref>

Other diseases that involve abnormal muscle fatigue (which may be described as exercise-induced muscle weakness, reversible muscle weakness, or muscle weakness that improves with rest) include: endocrine myopathies (such as [[Hoffmann syndrome|Hoffman syndrome]]), Tubular aggregate myopathy (TAM), [[ischemia]] (such as [[intermittent claudication]], [[popliteal artery entrapment syndrome]], and [[chronic venous insufficiency]]), and poor diet or malabsorption diseases that lead to [[vitamin D deficiency]] (osteomalic myopathy). Although limb-girdle muscular dystrophies (LGMDs) involve fixed muscle weakness, LGMDR8 also involves muscle fatigue;<ref>{{Cite web |title=MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 8; LGMDR8 |url=https://www.omim.org/entry/254110 |url-status=live |archive-url=https://web.archive.org/web/20240531123356/https://www.omim.org/entry/254110 |archive-date=31 May 2024 |access-date=2023-11-24 |website=www.omim.org }}</ref> as do some limb-girdle muscular dystrophy-dystroglycanopathies such as MDDGC3 (a.k.a. LGMDR15 and LGMD2O).<ref name=":3" /><ref>{{Cite web |title=MUSCULAR DYSTROPHY-DYSTROGLYCANOPATHY (LIMB-GIRDLE), TYPE C, 3; MDDGC3 |url=https://www.omim.org/entry/613157 |url-status=live |archive-url=https://web.archive.org/web/20230609063352/https://omim.org/entry/613157 |archive-date=9 June 2023 |access-date=2023-11-24 |website=www.omim.org }}</ref> Myofibrillar myopathy 10,<ref>{{Cite web |title=MYOFIBRILLAR MYOPATHY 10; MFM10 |url=https://www.omim.org/entry/619040 |url-status=live |archive-url=https://web.archive.org/web/20240421111521/https://omim.org/entry/619040 |archive-date=21 April 2024 |access-date=2023-11-24 |website=www.omim.org }}</ref> dimethylglycine dehydrogenase deficiency,<ref>{{Cite web |title=DIMETHYLGLYCINE DEHYDROGENASE DEFICIENCY; DMGDHD |url=https://www.omim.org/entry/605850 |url-status=live |archive-url=https://web.archive.org/web/20221014230504/https://omim.org/entry/605850 |archive-date=14 October 2022 |access-date=2023-11-24 |website=www.omim.org }}</ref> erythrocyte lactate transporter defect,<ref>{{Cite web |title=ERYTHROCYTE LACTATE TRANSPORTER DEFECT |url=https://www.omim.org/entry/245340 |url-status=live |archive-url=https://web.archive.org/web/20240513063740/https://www.omim.org/entry/245340 |archive-date=13 May 2024 |access-date=2023-11-24 |website=www.omim.org }}</ref> and myopathy with myalgia, increased serum creatine kinase, with or without episodic rhabdomyolysis (MMCKR)<ref>{{Cite web |title=MYOPATHY WITH MYALGIA, INCREASED SERUM CREATINE KINASE, AND WITH OR WITHOUT EPISODIC RHABDOMYOLYSIS; MMCKR |url=https://www.omim.org/entry/620138 |url-status=live |archive-url=https://web.archive.org/web/20240603103141/https://www.omim.org/entry/620138 |archive-date=3 June 2024 |access-date=2023-11-24 |website=www.omim.org }}</ref> also include muscle fatigue.

X-linked episodic muscle weakness (EMWX) includes general muscle weakness, ptosis, and fluctuations in strength. In some individuals, fatiguability was demonstrable, the phenotype having features comparable to congenital myasthenic syndromes and [[Channelopathy|channelopathies]].<ref>{{Cite web |title=EPISODIC MUSCLE WEAKNESS, X-LINKED; EMWX |url=https://www.omim.org/entry/300211 |url-status=live |archive-url=https://web.archive.org/web/20240703204110/https://www.omim.org/entry/300211 |archive-date=3 July 2024 |access-date=2023-11-24 |website=www.omim.org }}</ref>

Signs and symptoms of myasthenia presenting from infancy or childhood may be one of the [[congenital myasthenic syndrome]]s, which can be inherited in either an autosomal dominant or recessive manner. There are currently over two dozen types of congenital myasthenic syndromes.<ref>{{Cite web |title=Phenotypic Series - PS601462, PS610542 - Congenital myasthenic syndromes - OMIM |url=https://www.omim.org/phenotypicSeries/PS610542,PS601462 |url-status=live |archive-url=https://web.archive.org/web/20240703204110/https://www.omim.org/phenotypicSeries/PS610542,PS601462 |archive-date=3 July 2024 |access-date=2023-11-24 |website=www.omim.org}}</ref>

Limb–girdle myasthenia gravis is a distinct condition from myasthenia gravis. It is an adult-onset, autoimmune condition affecting the neuromuscular junction. However, it lacks eye abnormalities and is associated with autoimmune conditions such as systemic lupus erythematosus, Hashimoto's thyroiditis, and thymoma.<ref>{{Cite web |title=159400 - MYASTHENIA, LIMB-GIRDLE, AUTOIMMUNE - OMIM |url=https://www.omim.org/entry/159400 |url-status=live |archive-url=https://web.archive.org/web/20230602162212/https://omim.org/entry/159400 |archive-date=2 June 2023 |access-date=2024-02-29 |website=www.omim.org }}</ref>

[[Lambert–Eaton myasthenic syndrome]] (LEMS) is an autoimmune condition that attacks the neuromuscular junction, either as a paraneoplastic syndrome (typically older people) or associated with a non-cancerous primary autoimmune condition (typically younger people). It usually involves lower limb weakness and exercise-induced fatiguability, although the upper limbs and eyes may also be involved. Lambert's sign is the unusual improvement of grip strength that follows after squeezing the hand at maximum intensity for 2–3 seconds.<ref>{{Cite journal |last1=Pascuzzi |first1=Robert M. |last2=Bodkin |first2=Cynthia L. |date=2022 |title=Myasthenia Gravis and Lambert-Eaton Myasthenic Syndrome: New Developments in Diagnosis and Treatment |journal=Neuropsychiatric Disease and Treatment |volume=18 |pages=3001–3022 |doi=10.2147/NDT.S296714 |pmc=9792103 |pmid=36578903 |doi-access=free }}</ref>

==Management==
Treatment is by medication and/or surgery. Medication consists mainly of acetylcholinesterase inhibitors to directly improve muscle function and [[immunosuppressant drug]]s to reduce the autoimmune process.<ref name="auto1" /><ref name="Mehndiratta_2014">{{Cite journal |vauthors=Mehndiratta MM, Pandey S, Kuntzer T |date=October 2014 |title=Acetylcholinesterase inhibitor treatment for myasthenia gravis |journal=The Cochrane Database of Systematic Reviews |volume=2014 |issue=10 |article-number=CD006986 |doi=10.1002/14651858.CD006986.pub3 |pmc=7390275 |pmid=25310725}}</ref> [[Thymectomy]] is a surgical method to treat MG.<ref>{{Cite journal |vauthors=Gronseth GS, Barohn RJ |date=July 2000 |title=Practice parameter: thymectomy for autoimmune myasthenia gravis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology |journal=Neurology |volume=55 |issue=1 |pages=7–15 |doi=10.1212/wnl.55.1.7 |pmid=10891896 |doi-access=free}}</ref><ref name="pmid39434135">{{cite journal |vauthors=Gu J, Qiao Y, Huang R, Cong S |title=Efficacy and safety of immunosuppressants and monoclonal antibodies in adults with myasthenia gravis: a systematic review and network meta-analysis |journal=J Transl Med |volume=22 |issue=1 |article-number=955 |date=October 2024 |pmid=39434135 |pmc=11492773 |doi=10.1186/s12967-024-05751-1 |doi-access=free |url=}}</ref>

===Medication===
[[File:Neostigmine.svg|thumb|Neostigmine, chemical structure]]
[[File:Azathioprine.svg|thumb|Azathioprine, chemical structure]]
About 10% of people with generalized MG are considered [[Disease#Refractory disease|treatment-refractory]].<ref>{{Cite journal |vauthors=Suh J, Goldstein JM, Nowak RJ |date=June 2013 |title=Clinical characteristics of refractory myasthenia gravis patients |journal=The Yale Journal of Biology and Medicine |volume=86 |issue=2 |pages=255–60 |pmc=3670444 |pmid=23766745}}</ref> Autologous [[hematopoietic stem cell transplantation]] (HSCT) is sometimes used in severe, treatment-refractory MG. Available data provide preliminary evidence that HSCT can be an effective therapeutic option in carefully selected cases.<ref>{{Cite journal |vauthors=Burman J, Tolf A, Hägglund H, Askmark H |date=February 2018 |title=Autologous haematopoietic stem cell transplantation for neurological diseases |journal=Journal of Neurology, Neurosurgery, and Psychiatry |volume=89 |issue=2 |pages=147–155 |doi=10.1136/jnnp-2017-316271 |pmc=5800332 |pmid=28866625}}</ref>

[[Efgartigimod alfa]] (Vyvgart) was approved for medical use in the United States in December 2021.<ref name="FDA PR 20211217">{{citation-attribution|1={{Cite press release |title=FDA Approves New Treatment for Myasthenia Gravis |date=17 December 2021 |url=https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis |access-date=21 December 2021 |url-status=live |archive-url=https://web.archive.org/web/20211220222022/https://www.fda.gov/news-events/press-announcements/fda-approves-new-treatment-myasthenia-gravis |archive-date=20 December 2021 |website=U.S. [[Food and Drug Administration]] (FDA)}} }}</ref><ref>{{Cite press release |title=Argenx Announces U.S. Food and Drug Administration (FDA) Approval of Vyvgart (efgartigimod alfa-fcab) in Generalized Myasthenia Gravis |date=17 December 2021 |url=https://www.argenx.com/news/argenx-announces-us-food-and-drug-administration-fda-approval-vyvgarttm-efgartigimod-alfa-fcab |access-date=21 December 2021 |url-status=live |archive-url=https://web.archive.org/web/20211220195236/https://www.argenx.com/news/argenx-announces-us-food-and-drug-administration-fda-approval-vyvgarttm-efgartigimod-alfa-fcab |archive-date=20 December 2021 |website=Argenx}}</ref><ref>{{Cite press release |title=argenx Announces U.S. Food and Drug Administration (FDA) Approval of Vyvgart (efgartigimod alfa-fcab) in Generalized Myasthenia Gravis |date=17 December 2021 |publisher=Argenx |url=https://www.businesswire.com/news/home/20211217005641/en/argenx-Announces-U.S.-Food-and-Drug-Administration-FDA-Approval-of-VYVGART%E2%84%A2-efgartigimod-alfa-fcab-in-Generalized-Myasthenia-Gravis |via=Business Wire |access-date=21 December 2021 |url-status=live |archive-url=https://web.archive.org/web/20211219122355/https://www.businesswire.com/news/home/20211217005641/en/argenx-Announces-U.S.-Food-and-Drug-Administration-FDA-Approval-of-VYVGART%E2%84%A2-efgartigimod-alfa-fcab-in-Generalized-Myasthenia-Gravis |archive-date=19 December 2021}}</ref>

[[Efgartigimod alfa/hyaluronidase]] (Vyvgart Hytrulo) was approved for medical use in the United States in June 2023.<ref>{{Cite press release |title=Halozyme Announces argenx Receives FDA Approval for Vyvgart Hytrulo With Enhanze for Subcutaneous Use in Generalized Myasthenia Gravis |date=20 June 2023 |publisher=Halozyme Therapeutics |url=https://www.prnewswire.com/news-releases/halozyme-announces-argenx-receives-fda-approval-for-vyvgart-hytrulo-with-enhanze-for-subcutaneous-use-in-generalized-myasthenia-gravis-301855994.html |via=PR Newswire |access-date=24 June 2023 |url-status=live |archive-url=https://web.archive.org/web/20230624173634/https://www.prnewswire.com/news-releases/halozyme-announces-argenx-receives-fda-approval-for-vyvgart-hytrulo-with-enhanze-for-subcutaneous-use-in-generalized-myasthenia-gravis-301855994.html |archive-date=24 June 2023}}</ref><ref>{{Cite press release |title=Argenx Announces U.S. Food and Drug Administration Approval of Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) Injection for Subcutaneous Use in Generalized Myasthenia Gravis |date=20 June 2023 |url=https://www.argenx.com/news/argenx-announces-us-food-and-drug-administration-approval-vyvgart-hytrulo-efgartigimod-alfa |access-date=24 June 2023 |url-status=live |archive-url=https://web.archive.org/web/20230624190259/https://www.argenx.com/news/argenx-announces-us-food-and-drug-administration-approval-vyvgart-hytrulo-efgartigimod-alfa |archive-date=24 June 2023 |website=Argenx}}</ref>

[[Rozanolixizumab]] (Rystiggo) was approved for medical use in the United States in June 2023.<ref>{{Cite web |date=28 June 2023 |title=Novel Drug Approvals for 2023 |url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2023 |url-status=live |archive-url=https://web.archive.org/web/20230121035617/https://www.fda.gov/drugs/new-drugs-fda-cders-new-molecular-entities-and-new-therapeutic-biological-products/novel-drug-approvals-2023 |archive-date=21 January 2023 |access-date=28 June 2023 |website=U.S. [[Food and Drug Administration]] (FDA)}}</ref><ref>{{Cite press release |title=UCB announces U.S. FDA approval of Rystiggo (rozanolixizumab-noli) for the treatment of adults with generalized myasthenia gravis |date=27 June 2023 |publisher=UCB |url=https://www.prnewswire.com/news-releases/ucb-announces-us-fda-approval-of-rystiggo-rozanolixizumab-noli-for-the-treatment-of-adults-with-generalized-myasthenia-gravis-301864023.html |via=PR Newswire |access-date=28 June 2023 |url-status=live |archive-url=https://web.archive.org/web/20230628045311/https://www.prnewswire.com/news-releases/ucb-announces-us-fda-approval-of-rystiggo-rozanolixizumab-noli-for-the-treatment-of-adults-with-generalized-myasthenia-gravis-301864023.html |archive-date=28 June 2023}}</ref>

====Acetylcholinesterase inhibitors====
Acetylcholinesterase inhibitors can provide symptomatic benefit and may not fully remove a person's weakness from MG.<ref name="Mehndiratta_2014"/> While they might not fully remove all symptoms of MG, they still may allow a person the ability to perform normal daily activities.<ref name="Mehndiratta_2014" /> Usually, acetylcholinesterase inhibitors are started at a low dose and increased until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating, which is helpful for those who have difficulty swallowing due to their illness. Another medication used for MG, [[atropine]], can reduce the muscarinic side effects of acetylcholinesterase inhibitors.<ref>{{Cite web |date=2014 |title=Atropine – Myasthenia-gravis medicines and drugs |url=http://www.nhs.uk/medicine-guides/pages/MedicineOverview.aspx?condition=Myasthenia-gravis&medicine=Atropine |archive-url=https://web.archive.org/web/20150712212657/http://www.nhs.uk/medicine-guides/pages/MedicineOverview.aspx?condition=Myasthenia-gravis&medicine=Atropine |archive-date=12 July 2015 |access-date=2015-07-11 |publisher=NHS Choices}}</ref> [[Pyridostigmine]] is a relatively long-acting drug (when compared to other cholinergic agonists), with a half-life around four hours with relatively few side effects.<ref name=":1">{{Cite journal |vauthors=Kumar V, Kaminski HJ |date=February 2011 |title=Treatment of myasthenia gravis |journal=Current Neurology and Neuroscience Reports |volume=11 |issue=1 |pages=89–96 |doi=10.1007/s11910-010-0151-1 |pmid=20927659 }}</ref> Generally, it is discontinued in those who are being mechanically ventilated, as it is known to increase the amount of salivary secretions.<ref name=":1" /> A few high-quality studies have directly compared cholinesterase inhibitors with other treatments (or placebo); their practical benefit may be so significant that conducting studies in which they would be withheld from some people would be difficult.<ref name="Mehndiratta_2014"/>

====Immune suppressants====
The steroid [[prednisone]] might also be used to achieve a better result, but it can lead to the worsening of symptoms and takes weeks to achieve its maximal effectiveness.<ref name=":1" /> Research suggests that up to 15% of people with myasthenia gravis do not positively respond to immune suppressants.<ref>{{Cite journal |vauthors=Drachman DB, Adams RN, Hu R, Jones RJ, Brodsky RA |date=1 June 2008 |title=Rebooting the immune system with high-dose cyclophosphamide for treatment of refractory myasthenia gravis |journal=Annals of the New York Academy of Sciences |volume=1132 |issue=1 |pages=305–314 |bibcode=2008NYASA1132..305D |doi=10.1196/annals.1405.033 |pmc=3390145 |pmid=18567882}}</ref><ref>{{Cite journal |vauthors=Suh J, Goldstein JM, Nowak RJ |date=June 2013 |title=Clinical characteristics of refractory myasthenia gravis patients |journal=The Yale Journal of Biology and Medicine |volume=86 |issue=2 |pages=255–260 |pmc=3670444 |pmid=23766745}}</ref><ref name="auto1" /> Due to the myriad symptoms that steroid treatments can cause, it is not the preferred method of treatment.<ref name=":1" /> Other immune suppressing medications may also be used including [[rituximab]]<ref>{{Cite journal |vauthors=Tandan R, Hehir MK, Waheed W, Howard DB |date=August 2017 |title=Rituximab treatment of myasthenia gravis: A systematic review |journal=Muscle & Nerve |volume=56 |issue=2 |pages=185–196 |doi=10.1002/mus.25597 |pmid=28164324 }}</ref> or [[azathioprine]].<ref name="NIH2016" />

[[Nipocalimab]] (Imaavy) was approved for medical use in the United States in April 2025.<ref>{{cite web | title=Novel Drug Approvals for 2025 | website=U.S. [[Food and Drug Administration]] (FDA) | date=1 May 2025 | url=https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025 | archive-url=https://web.archive.org/web/20250303200027/https://www.fda.gov/drugs/novel-drug-approvals-fda/novel-drug-approvals-2025 | url-status=live | archive-date=3 March 2025 | access-date=1 May 2025}}</ref><ref name="JandJ PR 20250430">{{cite press release | title=Johnson & Johnson receives FDA approval for Imaavy (nipocalimab-aahu), a new FcRn blocker offering long-lasting disease control in the broadest population of people living with generalized myasthenia gravis (gMG) | publisher=Johnson & Johnson | via=MultiVu | date=30 April 2025 | url=https://www.multivu.com/johnson-johnson/9331651-en-johnson-johnson-receives-fda-approval-imaavy-nipocalimab-aahu | access-date=1 May 2025 | archive-date=1 May 2025 | archive-url=https://web.archive.org/web/20250501045018/https://www.multivu.com/johnson-johnson/9331651-en-johnson-johnson-receives-fda-approval-imaavy-nipocalimab-aahu | url-status=live }}</ref>

===Plasmapheresis and IVIG===
If the myasthenia is serious (myasthenic crisis), [[plasmapheresis]] can be used to remove the putative antibodies from the circulation. Also, [[intravenous immunoglobulin]]s (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks, and often are associated with high costs, which make them prohibitive; they are generally reserved for when MG requires hospitalization.<ref name=":1" /><ref name="Juel2004">{{Cite journal |vauthors=Juel VC |date=March 2004 |title=Myasthenia gravis: management of myasthenic crisis and perioperative care |journal=Seminars in Neurology |volume=24 |issue=1 |pages=75–81 |doi=10.1055/s-2004-829595 |pmid=15229794 }}</ref>

===Surgery===
As [[thymoma]]s are seen in 10% of all people with the MG, they are often given a chest X-ray and CT scan to evaluate their need for surgical removal of their thymus glands and any cancerous tissue that may be present.<ref name="Rosen2014" /><ref name=":2" /> Even if surgery is performed to remove a thymoma, it generally does not lead to the remission of MG.<ref name=":1" /> Surgery in the case of MG involves the removal of the thymus, although in 2013, no clear benefit was indicated except in the presence of a thymoma.<ref name="Cea2013">{{cite journal |last1=Cea |first1=Gabriel |last2=Benatar |first2=Michael |last3=Verdugo |first3=Renato J |last4=Salinas |first4=Rodrigo A |title=Thymectomy for non-thymomatous myasthenia gravis |journal=Cochrane Database of Systematic Reviews |date=14 October 2013 |volume=2013 |issue=10 |article-number=CD008111 |doi=10.1002/14651858.CD008111.pub2 |pmid=24122674 |pmc=12083877 }}</ref> A 2016 randomized, controlled trial, however, found some benefits.<ref>{{Cite journal |display-authors=6 |vauthors=Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Ströbel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A, Newsom-Davis J, Cutter GR |date=August 2016 |title=Randomized Trial of Thymectomy in Myasthenia Gravis |journal=The New England Journal of Medicine |volume=375 |issue=6 |pages=511–522 |doi=10.1056/NEJMoa1602489 |pmc=5189669 |pmid=27509100 |hdl=2318/1601939}}{{Erratum|doi=10.1056/NEJMx170003|pmid=28471717|http://retractionwatch.com/2017/06/20/big-corrections-usually-weaken-findings-recent-nejm-one-strengthened-author-says/ ''Retraction Watch''|checked=yes}}</ref>

===Physical measures===
People with MG should be educated regarding the fluctuating nature of their symptoms, including weakness and exercise-induced fatigue. Exercise participation should be encouraged with frequent rest.<ref name="Goldenberg" /> In people with generalized MG, some evidence indicates a partial home program including training in [[diaphragmatic breathing]], [[pursed-lip breathing]], and interval-based muscle therapy may improve respiratory muscle strength, chest wall mobility, respiratory pattern, and respiratory endurance.<ref>{{Cite journal |vauthors=Cup EH, Pieterse AJ, Ten Broek-Pastoor JM, Munneke M, van Engelen BG, Hendricks HT, van der Wilt GJ, Oostendorp RA |date=November 2007 |title=Exercise therapy and other types of physical therapy for patients with neuromuscular diseases: a systematic review |journal=Archives of Physical Medicine and Rehabilitation |volume=88 |issue=11 |pages=1452–1464 |doi=10.1016/j.apmr.2007.07.024 |pmid=17964887}}</ref>

===Medical imaging===
In people with myasthenia gravis, older forms of [[iodinated contrast]] used for medical imaging have caused an increased risk of exacerbation of the disease, but modern forms have no immediate increased risk.<ref name="MehriziPascuzzi2014">{{Cite journal |vauthors=Mehrizi M, Pascuzzi RM |date=September 2014 |title=Complications of radiologic contrast in patients with myasthenia gravis |journal=Muscle & Nerve |volume=50 |issue=3 |pages=443–4 |doi=10.1002/mus.24254 |pmid=24677227 }}</ref>

==Prognosis==
The prognosis of people with MG is generally good, as is quality of life, when given very good treatment.<ref>{{Cite journal |vauthors=Sieb JP |date=March 2014 |title=Myasthenia gravis: an update for the clinician |journal=Clinical and Experimental Immunology |volume=175 |issue=3 |pages=408–418 |doi=10.1111/cei.12217 |pmc=3927901 |pmid=24117026}}</ref> Monitoring of a person with MG is very important, as at least 20% of people diagnosed with it will experience a myasthenic crisis within two years of their diagnosis, requiring rapid medical intervention.<ref name=":1" /> Generally, the most disabling period of MG might be years after the initial diagnosis.<ref name="Mehndiratta_2014" /> Assistive devices may be needed to assist with mobility.<ref name="NIH2016" /> In the early 1900s, 70% of detected cases died from lung problems; now, that number is estimated to be around 3–5%, an improvement attributed to increased awareness and medications to manage symptoms.<ref name=":1" />

==Epidemiology==
MG occurs in all ethnic groups and both sexes. It most commonly affects women under 40 and people from 50 to 70 years old of either sex, but it has been known to occur at any age. Younger people rarely have thymoma. [[Prevalence]] in the United States is estimated at between 0.5 and 20.4 cases per 100,000, with an estimated 60,000 Americans affected.<ref name="Rosen2014" /><ref name="Cea2013"/> In the United Kingdom, an estimated 15 cases of MG occur per 100,000 people.<ref name=":2" /> The [[mortality rate]] of MG is around 5-9%.<ref>{{Cite journal |last1=Dresser |first1=Laura |last2=Wlodarski |first2=Richard |last3=Rezania |first3=Kourosh |last4=Soliven |first4=Betty |date=21 May 2021 |title=Myasthenia Gravis: Epidemiology, Pathophysiology and Clinical Manifestations |journal=Journal of Clinical Medicine |volume=10 |issue=11 |page=2235 |doi=10.3390/jcm10112235 |pmc=8196750 |pmid=34064035 |doi-access=free }}</ref>

==History==
The first to write about MG were [[Thomas Willis]], [[Samuel Wilks]], Erb, and Goldflam.<ref name="Nair2014">{{Cite journal |vauthors=Nair AG, Patil-Chhablani P, Venkatramani DV, Gandhi RA |date=October 2014 |title=Ocular myasthenia gravis: a review |journal=Indian Journal of Ophthalmology |volume=62 |issue=10 |pages=985–991 |doi=10.4103/0301-4738.145987 |pmc=4278125 |pmid=25449931 |doi-access=free}}</ref> The term "myasthenia gravis pseudo-paralytica" was proposed in 1895 by Jolly, a German physician.<ref name="Nair2014" /> [[Mary Broadfoot Walker|Mary Walker]] treated a person with MG with [[physostigmine]] in 1934.<ref name="Nair2014" /> Simpson and Nastuck detailed the autoimmune nature of the condition.<ref name="Nair2014" /> In 1973, Patrick and Lindstrom used rabbits to show that immunization with purified muscle-like acetylcholine receptors caused the development of MG-like symptoms.<ref name="Nair2014" />

==Research==
Immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched.<ref name="Losen2008">{{Cite journal |vauthors=Losen M, Martínez-Martínez P, Phernambucq M, Schuurman J, Parren PW, De Baets MH |year=2008 |title=Treatment of myasthenia gravis by preventing acetylcholine receptor modulation |journal=Annals of the New York Academy of Sciences |volume=1132 |issue=1 |pages=174–179 |bibcode=2008NYASA1132..174L |doi=10.1196/annals.1405.034 |pmid=18567867 }}</ref> Some research recently has been on [[Complement component 5|anti-c5 inhibitors]] for treatment research as they are safe and used in the treatment of other diseases.<ref name="auto2" /> [[Ephedrine]] seems to benefit some people more than other medications, but it has not been properly studied as of 2014.<ref name="ReferenceA" />
In the laboratory, MG is mostly studied in model organisms, such as rodents. In addition, in 2015, scientists developed an ''in vitro'' functional, all-human, [[neuromuscular junction]] assay from human [[embryonic stem cell]]s and somatic-muscle stem cells. After the addition of pathogenic antibodies against the acetylcholine receptor and activation of the [[complement system]], the neuromuscular co-culture shows symptoms such as weaker muscle contractions.<ref>{{Cite journal |vauthors=Steinbeck JA, Jaiswal MK, Calder EL, Kishinevsky S, Weishaupt A, Toyka KV, Goldstein PA, Studer L |date=January 2016 |title=Functional Connectivity under Optogenetic Control Allows Modeling of Human Neuromuscular Disease |journal=Cell Stem Cell |volume=18 |issue=1 |pages=134–143 |doi=10.1016/j.stem.2015.10.002 |pmc=4707991 |pmid=26549107}}</ref> Recent years, scientists have been working on finding the reliable [[biomarker]]s for MG to monitor the disease development and assess the severity.

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{Cite journal |vauthors=Zhang Z, Guo J, Su G, Li J, Wu H, Xie X |date=17 November 2014 |title=Evaluation of the quality of guidelines for myasthenia gravis with the AGREE II instrument |journal=PLOS ONE |volume=9 |issue=11 |article-number=e111796 |bibcode=2014PLoSO...9k1796Z |doi=10.1371/journal.pone.0111796 |pmc=4234220 |pmid=25402504 |doi-access=free}}
* {{Cite web |title=Diagnostic: Myasthenia gravis |url=https://www.ncbi.nlm.nih.gov/gtr/conditions/C0026896/ |url-status=live |archive-url=https://web.archive.org/web/20171210102710/https://www.ncbi.nlm.nih.gov/gtr/conditions/C0026896/ |archive-date=10 December 2017 |access-date=2015-07-11 |website=National Center for Biotechnology Information (NCBI) |publisher=U.S. National Library of Medicine}}
{{refend}}

==External links==
{{Commons}}
* [https://myasthenia.org/ Myasthenia Gravis Foundation of America (MGFA)]
* [https://myastheniagravisnews.com/ Myasthenia Gravis News]
* [https://www.myaware.org/ myaware.org]
* [https://myastheniagravis.org/ Conquer MG]

{{Medical resources
| DiseasesDB     = 8460
| ICD11          = {{ICD11|8C60}}
| ICD10          = {{ICD10|G70.0}}
| ICD9           = {{ICD9|358.0}}, {{ICD9|358.01}} (in crisis)
| ICDO           =
| OMIM           = 254200
| MedlinePlus    = 000712
| eMedicineSubj  = neuro
| eMedicineTopic = 232
| eMedicine_mult = {{eMedicine2|emerg|325}} (emergency), {{eMedicine2|med|3260}} (pregnancy), {{eMedicine2|oph|263}} (eye)
| MeshID         = D009157
| Orphanet       = 589
| Scholia        = Q8285
}}
{{Diseases of myoneural junction and muscle}}
{{Autoimmune diseases}}
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{{Authority control}}

{{DEFAULTSORT:Myasthenia Gravis}}
[[Category:Autoimmune diseases]]
[[Category:Myoneural junction and neuromuscular diseases]]
[[Category:Wikipedia medicine articles ready to translate]]
[[Category:Wikipedia neurology articles ready to translate]]